Skeletal remodelling may be defined as the balanced interaction of the processes of bone formation and resorption in the adult animal. Disruption of this balance results in a number of skeletal disorders such as, osteoporosis, osteopetrosis and osteosclerosis. The essential mechanisms underlying the remodelling process have to do with the regulation of bone matrix synthesis and degradation. It has been known for many years that the cell in bone responsible for synthesizing matrix is the osteoblast. Recently, a body of information has accrued indicating that the osteoblast plays a pivotal role in bone resorption as well as formation. This has included its identification as the target and mediatory cell for many bone- resorbing agents, in particular, parathyroid hormone (PTH). One consequence of PTH action is a reduction in the synthesis of type I collagen, the major organic component of bone matrix. In previous and preliminary studies, we have confirmed this observation using the osteoblastic tumor cell line, UMR 106-01. Specifically, we have found that exposure of UMR cells to PTH results in a 40% decline in the rate of collagen synthesis and a 95% reduction in procollagen mRNA abundance. Moreover, in nuclear runoff and procollagen chimeric gene transient transfection experiments, we have established that the latter reduction in message level is not due to PTH-induced alterations in transcriptional activity leading us to formulate the hypothesis that PTH regulates gene expression in UMR cells by controlling messenger stability. The aims of the present proposal are to test and clarify this hypothesis by, 1) directly measuring procollagen mRNA half-life in control and PTH-treated cells. 2) assessing whether such messenger degradation occurs in ribonucleoprotein (RNP) particles, free polysomes or polysomes associated with the endoplasmic reticulum and whether there is localization of procollagen transcripts to any of these compartments, 3) investigating whether protein synthesis is an obligate part of the mRNA degradation process and, if so, 4) determining whether a specific "RNase" is responsible for procollagen transcript turnover, and, finally, 5) testing whether it is cAMP, diacylglcerol or Ca2+ that is the effective second messenger of PTH in regulating procollagen mRNA abundance and stability. Our overall goal, the determination of the site and mechanism of turnover of collagen transcripts, should shed light on the action of PTH on the osteoblast.